Anti-Inhibitor Coagulant Complex, Vapor Heated – FEIBA VH Immuno
Status – approved; marketed
Organizations involved:
Baxter Hyland Immuno – World mark.
Baxter AG – Manuf.; R&D; Tech.
Baxter Healthcare Corp. – Parent co.
Cross ref: See the Factor VIII Products entry (#715) for discussion of Factor VIII inhibitors. See also the entries for Anti-Inhibitor Coagulant Complex, Heat Treated (Autoplex T) (#705); and Prothrombin Complex (Octaplex) (#805).
Description: Anti-Inhibitor Coagulant Complex, Heat Treated or FEIBA VH Immuno is a lyophilized (freeze-dried) formulation obtained from pooled fractionated Plasma (Human) containing primarily non-activated Factor VII zymogen and other coagulation/clotting factors, with manufacture including viral inactivation by vapor heat treatment (pasteurization). FEIBA stands for “factor eight inhibitor bypassing activity,” descriptive of the its ability to treat hemophilia A in patients with inhibitors (Factor VIII neutralizing antibodies).
Anti-Inhibitor Coagulation Complex contains a mixture of human plasma-derived clotting factors that do not stimulate the immune system to induce antibodies to Factor VIII or cross-react with Factor VIII inhibitors (antibodies). The coagulation factors in this mixture are partially activated during manufacture through a controlled activation step. FEIBA VH mainly contains non-activated Factor VII and also Factors II, IX, and X, along with activated forms of Factors VII and X (and possibly Factors II and IX). The activated Factor VII and Factor X (VIIa and Xa) in the complex can produce a fibrin clot without the need for Factor VIII or Factor IX. The clotting activity unit associated with Anti-Inhibitor Coagulation Complex is often referred to as a “bypassing activity unit.”
FEIBA VH is packaged in vials containing 400-1,200 IU. FEIBA VH contains approximately equal units of Factor VIII inhibitor bypassing activity and Prothrombin Complex Factors. In addition, 1-6 units of Factor VIII coagulant antigen (Factor VIII C:Ag) per mL are present. The preparation contains only traces of factors of the kinin generating system and no heparin. Reconstituted FEIBA VH Immuno also contains 4 mg of trisodium citrate and 8 mg of sodium chloride per mL. FEIBA VH Immuno is supplied in a vial along with suitable volume of Sterile Water for Injection, USP., a sterile double-ended needle, and a sterile filter needle. The product should be stored at 2-8˚C refrigerated.
Potency of Factor VIII bypassing activity is based on the product’s ability to the correct clotting time of hemophilic plasma in the presence of inhibitors of Factor VIII (Factor VIII antibodies). A lyophilized reference standard is used. The unit of activity is defined by the reference standard and is approximately the amount needed to correct the partial thromboplastin time of hemophilic plasma. The Factor VIII inhibitor bypassing activity of FEIBA VH is expressed in arbitrary units unique to this product. One IMMUNO Unit of activity is defined as that amount of FEIBA VH that shortens the activated partial thromboplastin time (APTT; a measure of clotting time) of a high titer Factor VIII inhibitor reference plasma to 50% of the blank value. The number of IMMUNO Units of Factor VIII inhibitor bypassing activity is stated on each bottle. Nomenclature: Anti-Inhibitor Coagulant/Baxter [BIO]; FEIBA VH Immuno [TR]; Anti-Inhibitor Coagulant Complex [FDA]; Anti-Inhibitor Coagulant Complex, Vapor Heated [FDA used on product insert/labeling]
Companies.: FEIBA VH Immuno was developed and is manufactured by Oesterreichisches Institut fur Haemoderivate GmbH (OIH), formerly a subsidiary of Immuno AG (Vienna, Austria), now Baxter AG, a subsidiary of Baxter Hyland Immuno, FDA CBER est. lic. no. 0258. It is marketed in the U.S. by Baxter Hyland Immuno, and internationally by Baxter Hyland Immuno affiliates.
Manufacture: FEIBA VH Immuno is prepared from Source Plasma and/or Plasma. Cryoprecipitate supernatant undergoes controlled generation of FEIBA. The product is subjected to in-process virus inactivation in which vapor is first applied for 10 hours at 60˚ ± 0.5˚C at an excess pressure of 190 ± 20 mbar, followed by 1 hour at 80˚ ± 0.5˚C at an excess pressure of 370 ± 30 mbar. The product is filled in to vials and lyophilized.
In a preclinical study to determine the virus inactivating efficacy of vapor heating, samples spiked with 2 x 106 (2 million) infectious units of HIV per mL were subjected to vapor heat treatment. The residual virus titer was found to be less than 1 infectious unit/0.5 mL.
FDA class: Biologic PLA
Approvals: Date = 19820914; first approval, PLA, granted to Oesterreichisches Institut fur Haemoderivate GmbH (OIH)
Indications: [portions of the "INDICATIONS AND USAGE” section of product insert/labeling]:
Anti-Inhibitor Coagulant Complex, Vapor Heated, FEIBA VH IMMUNO is indicated for the control of spontaneous bleeding episodes or to cover surgical interventions in hemophilia A and B patients with inhibitors.
Clinical experience suggests that patients with a Factor VIII inhibitor titer of less than 5 B.U. may be successfully treated with Antihemophilic Factor. Patients with titers ranging between 5 and 10 B.U. may either be treated with Antihemophilic Factor or Anti-Inhibitor Coagulant Complex, Vapor Heated, FEIBA VH IMMUNO. Cases with Factor VIII inhibitor titers greater than 10 B.U. have generally been refractory to treatment with Antihemophilic Factor.
Medical: The in vivo half-lives of Factors VIIa and Xa in blood are relatively short. However, because Factor VII and Factor X in FEIBA VH exist in both the activated and non-activated forms, one dose of the product lasts for about 12 hours, with the non-activated forms serving as a “factor reserve” that the body can activate as needed. FEIBA VH shortens the activated partial thromboplastin time (APTT; clotting time) of plasma containing Factor VIII inhibitors. The product is intended for intravenous administration.
Market: The 2007 Average Wholesale Price (AWP) is $1.79/unit for either size vial (Red Book, 2007).
The estimated Acquisition Costs (for hospitals, treatment centers) has been reported to be $0.96-$1.15/IU [from NHF]. Medicare reimbursement is set at $1.43/IU for inpatient and home care, and $1.01/IU for outpatient care.
Companies involvement:
Full monograph
704 Anti-Inhibitor Coagulant/Baxter
Nomenclature:
Anti-Inhibitor Coagulant/Baxter [BIO]
FEIBA VH Immuno [TR]
Anti-Inhibitor Coagulant Complex [FDA]
Anti-Inhibitor Coagulant Complex, Vapor Heated [FDA used on product insert/labeling]
FDA Class: Biologic PLA
Year of approval (FDA) = 1982
Date of 1st FDA approval = 19820914
(in format YYYYMMDD)
Index Terms:
biopharmaceutical products
blood products
human materials used<!-- humansource -->
Factor VIII inhibitor bypassing activity
Anti-Inhibitor Coagulant Complex ref. standard
ethanol
Factor IX
Factor VII
Factor VIII coagulant antigen (F VIII C:Ag)
heat treatment (pasteurization)
lyophilized (freeze-dried)
Plasma (Human)
prothrombin, human
sodium chloride
Sterile Water for Injection
approval dates uncertain (FDA reports erroneous, conflicting, or simply has lost the original approval dates) (FDAapproved)
EU200 Currently Approved in EU
UM001 Marketed Product in US
US200 Currently Approved in US
EM001 Marketed Product in EU
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